Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great...Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.展开更多
Objective: To explore the mechanical behavior of lumbar spine loaded by stress and provide the mechanical basis for clinical analysis and judgement of lumbar spine fracture classification, mechanical distribution and...Objective: To explore the mechanical behavior of lumbar spine loaded by stress and provide the mechanical basis for clinical analysis and judgement of lumbar spine fracture classification, mechanical distribution and static stress. Methods: By means of computer simulation method, the constructed lumbar spine three-dimensional model was introduced into three-dimensional finite element analysis by software Ansys 7.0. The lumbar spine mechanical behavior in different parts of the stress loading were calculated. Impact load is 0-8000 N. The peak value was 8000 N. The loading time is 0-40 minutes. The values of the main stress, stress distribution and the lumbar spine unit displacement in the direction of main stress were analyzed. Results: The lumbar spine model was divided into a total of 121 239 nodes, 112 491 units. It could objectively reflect the true anatomy of lumbar spine and its biomechanical behavior and obtain the end-plate images under different stress. The stress distribution on the lumbar intervertebral disc (L3-L4) under the axial, lateral flexion and extension stress, and the displacement trace of the corresponding processus articularis were analyzed. Conclusion: It is helpful to analyze the stress distribution of lumbar spine and units displacement in static stress loading in the clinical research of lumbar spine injury and the distribution of internal stress.展开更多
文摘Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.
文摘Objective: To explore the mechanical behavior of lumbar spine loaded by stress and provide the mechanical basis for clinical analysis and judgement of lumbar spine fracture classification, mechanical distribution and static stress. Methods: By means of computer simulation method, the constructed lumbar spine three-dimensional model was introduced into three-dimensional finite element analysis by software Ansys 7.0. The lumbar spine mechanical behavior in different parts of the stress loading were calculated. Impact load is 0-8000 N. The peak value was 8000 N. The loading time is 0-40 minutes. The values of the main stress, stress distribution and the lumbar spine unit displacement in the direction of main stress were analyzed. Results: The lumbar spine model was divided into a total of 121 239 nodes, 112 491 units. It could objectively reflect the true anatomy of lumbar spine and its biomechanical behavior and obtain the end-plate images under different stress. The stress distribution on the lumbar intervertebral disc (L3-L4) under the axial, lateral flexion and extension stress, and the displacement trace of the corresponding processus articularis were analyzed. Conclusion: It is helpful to analyze the stress distribution of lumbar spine and units displacement in static stress loading in the clinical research of lumbar spine injury and the distribution of internal stress.